NRAP p.Pro1255=
c.3765C>T · VCV4909637
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00814%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -5.3 |
| Overall | ||
| CADD | 0.136 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00814%
European (non-Finnish) · 96/1,179,984 alleles
Filtering AF
0.00681%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00633%
Overall
0.00663%
107/1,614,010 alleles · very rare
exomes 94/1,461,832 · genomes 13/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00814% | 12,292 |
| East Asian | 0.00668% | 14,968 |
| African / African-American | 0.00534% | 18,727 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| Finnishnot grpmax-eligible | 0.00156% | 64,034 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- NRAP
- Protein
- p.Pro1255=
- Coding
- c.3765C>T
- MANE Select
- NM_198060
- Type
- single nucleotide variant
- Location
- chr10:113606220 (GRCh38)
- Gene constraint
- LOEUF 1.045 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 51.98
Similar variants
- NRAP p.Arg1037Ter Pathogenic/Likely pathogenic ★★ same type
- NRAP p.Trp1033Ter Pathogenic/Likely pathogenic ★★ same type
- NRAP c.360+1G>A Uncertain significance ★★ same type
- NRAP p.Ala29Gly Uncertain significance ★★ ⚠ same type
- NRAP p.Ala571Thr Uncertain significance ★★ same type
- NRAP p.Arg1330Gln Uncertain significance ★★ ⚠ same type
- NRAP p.Arg1559Gln Uncertain significance ★★ ⚠ same type
- NRAP p.Arg428Cys Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/nrap-p-pro1255 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown